Clinical development of moricizine as an antiarrhythmic agent.

The primary development of moricizine as an antiarrhythmic agent has occurred in the Soviet Union and the United States. The data in this presentation are based on the 1,844 subjects/patients (1,817 adults and 27 pediatric patients) who participated in 34 controlled studies and 3 uncontrolled compassionate-use programs conducted in the United States. Of the 1,817 adults, 443 received only placebo or comparative agents and 1,374 received moricizine in daily doses of 50 to 1,800 mg. A total of 1,190 adult patients (mean age 59 years) had ventricular arrhythmias classified as either benign (8%), potentially lethal (58%) or lethal (33%). Most patients had a history of greater than or equal to 1 cardiovascular disease, including coronary artery disease, previous myocardial infarction and congestive heart failure. Antiarrhythmic activity was assessed by four methods: 24-hour ambulatory electrocardiographic monitoring, programmed electrical stimulation, exercise tolerance tests, and global evaluation (only for some patients in the compassionate-use program). In addition, the effects of moricizine on symptoms associated with ventricular arrhythmias were assessed. The safety variables evaluated included adverse experiences, proarrhythmia, congestive heart failure, other cardiovascular effects, death, chest x-ray, ophthalmic examinations, neuroleptic phenothiazine effects and clinical laboratory tests.